GRDDS

1. SEMINAR ON
GASTRO RETENTIVE DRUG
DELIVERY SYSTEM
GRDDS
Dr. Gajanan S. Sanap M.Pharm.,Ph.D
Department of Pharmaceutics
Ideal College of Pharmacy and Research
Kalyan 421- 306

2. Presentation Outline....
 Introduction
 Advantages
 Gastro-retentive technologies
 Evaluation of GRDDS
 Disadvantages
 References

3. Introduction
Conventional oral drug delivery system (DDS) is
complicated by limited gastric residence time
(GRT).
Rapid GI transit can prevent complete drug
release in absorption zone & reduce the efficacy
of the administered dose since the majority of
drugs are absorbed in stomach or the upper part of
small intestine.

4. To overcome these limitations, various
approaches have been proposed to increase
gastric residence of drug delivery systems in
the upper part of GIT includes gastro retentive
drug delivery system (GRDDS).
Among the GRDDS, floating drug delivery
system (FDDS) have been the most commonly
used.

5.  Gastro-retentive delivery is one of the site
specific delivery of the drugs at stomach. It is
obtained by retaining dosage form into
stomach and drug is being released at
sustained manner to specific site either in
stomach or intestine.

6. Differ from Conventional Release…
Conventional Release GRDDS
Absorption
window

7. Advantages…
 Delivery of drugs with narrow absorption window in
the small intestine region.
 Longer residence time in the stomach could be
advantageous for local action in stomach, for
example treatment of peptic ulcer disease.
 Bio-availability can be improved.

8.  Reduced Frequency of Dosing with improved
patient compliance
 Minimize the Fluctuation of drug
concentrations
 Site specific drug delivery
 Enhances the Pharmacological effects

9. Candidates for GRDDS
 Drugs acting locally in the stomach E.g. Antacids
 Drugs that are principally absorbed in the stomach
 Drugs that are poorly soluble at the alkaline pH
 Drugs with a narrow window of absorption E.g.
Furosemide
 Drugs absorbed readily from the GI tract
 Drugs that degrade in the colon
 Drugs with variable Bioavailability
 Drugs with less half life

10. Non -
Effervescent
System
Effervescent
System
High density
systems
Swellable/
Expandable
systems Muco-
adhesive
systems
Low-density
systems
(Floating
drug
delivery)
Gastro Retentive Technologies

11. A) Low Density Approach
(Floating Drug Delivery)
 Retained in stomach
 Useful for poorly water
soluble OR unstable in intestinal
Fluid
 Bulk density : Less than
gastric fluid, so remain buoyant
in the stomach without affecting
gastric emptying rate for
prolonged period of time
 So drug release slowly at the
desired rate from system

12. Drugs those are...
 Primarily absorbed in the stomach
 Poorly soluble at an alkaline pH
 Narrow window of absorption
 Degrade in colon
Advantages of Low Density Approach OR
Floating Drug Delivery

13.  When there is a vigorous intestinal movement
and a short transit time as might occur in
certain type of diarrhoea, poor absorption is
expected. Under such circumstances it may be
advantageous to keep the drug in floating
condition in stomach to get a relatively better
response.

14.  Not feasible for those drugs that have
solubility OR stability problem in GIT
Require high level of fluid in stomach
 The drugs that may irritate the stomach lining
OR are unstable in acidic environment
 The dosage form should be administered with
a full glass of water (200-250 ml)
Disadvantages of Low Density Approach
OR
Floating Drug Delivery

15. B) Swellable System
Also called ‘ PLUG SYSTEM’
Size of the formulation more
than Pyloric sphincter
It should expand for gastric
retention Should be
Collapsed after lag time

16. Time

17. Picture of tablet in Dry and Wetted state

18.  The Dosage form must maintain a size larger
than pyloric sphincter
 The Dosage form must resist premature
gastric emptying
Disadvantages of Swelling System

19. C) Bio/Muco Adhesive System
Here, the drug is incorporated with bio/
Muco-adhesive agents, enabling the
Device to adhere to the stomach walls,
Thus resisting gastric emptying.
However, the mucus on the walls of
the Stomach is in a state of constant
renewal, Resulting in unpredictable
adherence.
Thus, this approach is not widely used.

20. Chitosan
Polyacrylic acid
Carbopol 934P, 971P, 980
Sodium alginate
HPMC K4M, K15M, K100M
Hydroxypropylcellulose (HPC)
Cholestyramine
Bio/Muco Adhesive Polymers

21. Rapid removal of mucus.
We are not sure weather the DF will adhere to
the mucus or epithelial cell layer
DF may adhere to esophagus resulting in drug
induced injuries
Problem of Muco-adhesive System

22. D) High Density Approch
Density should be more then
stomach content i.e. 3 g/cm3
Capable to withstand with
peristaltic movement of
stomach
Prepared by coating or mixing
drug with heavy inert material

23. Diluents such as…
 barium sulphate (density = 4.9),
 zinc oxide,
 titanium dioxide,
 iron powder
must be used to manufacture such high-density
formulations.

24.  Higher amount of drug require
The dosage form must stand with peristaltic
movement of stomach
Problem with High Density
Approch

25. Evaluation of GRDDS
GRDDS
Hardness Friability
Drug
Content
Diameter
Weight
Variation

26. Evaluation of GRDDS
 Dissolution
medium : 0.1 N HCl
 Temp. : 37 ± 0.5°C
 RPM : 50-100
 Sample analysis :
UV
 Dissolution Study

27.  In-vitro
Mucoadhesion
 Apparatus : USP
type VI (rotating
cylinder apparatus)
 Medium : 0.1 N HCl
 Temp. : 37 ± 0.5°C
 RPM : 100
Evaluation of GRDDS

28.  Lag time :
 Measurement : 0.1 N HCl at pH 1.2
 Temp. : 37 ± 0.5°C
 Apparatus : USP Type II dissolution apparatus
 A tablet is placed in a beaker containing 100 –
200 ml dissolution medium & the time for a
tablet to emerge on to the surface of the
dissolution medium is known as lag time .
Evaluation of GRDDS

29.  Floating Time
 After achieving lag time, the time taken for a tablet
to remain float on the surface of the dissolution
medium is called floating time.
Evaluation of GRDDS

30.  Water uptake :
 Apparatus : USP type II dissolution apparatus
 Medium : Water
 Temp. : 37 ± 0.5°C
 RPM : 50
WU (%) = Wt. of swollen tab. – Initial wt. of tab.
Initial wt. of tab. × 100
Evaluation of GRDDS

31. Evaluation of GRDDS
 In vitro Mucoadhesive strength

32.  It is not recommended for drugs which are
unstable at gastric/acidic pH, insoluble or very
low soluble drugs and drugs which causes
gastric irritation.
 For floating, high level of fluid is required in
GIT. Also sleeping condition is favorable for
the better results of GRDDS.
Limitation of GRDDS

33.  Bioadhesive systems, cannot prevail longer due to
high turn-over rate of mucus layer and presence of
soluble mucin
 For swelling systems, it is necessary that the
formulation should not exit before the appropriate
swelling
 For High density systems, High amount of drug is
require
Limitation of GRDDS

34. References
• Doshi S.M., Tank H.M., Gastro Retention – An Innovation
over Conventional poorly Soluble Drugs : A review,
International Journal of Pharmaceutical and chemcal Sciences,
2012;1(2):859-866.
• S. P. Vyas, Roop K. Khar, CONTROLLED DRUG
DELIVERY – Concepts & Advances, Vallabh Prakashan, page
no. 196-217.
• N. K. Jain, Progress in Controlled & Novel Drug Delivery
Systems, 1st edition 2004, CBS Publishers, page no.76-97
• G. Chawla, P. Gupta, V. Koradia, A. K. Bansal, Pharmaceutical
Technology July 2003, 50-68

35. Be Useful to Others
But
Never Be Used By
Others